Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes
Summary: Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the histone modification landscape is challenged by incorporation of new unmodified histones during each...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719317176 |
| _version_ | 1818541841340956672 |
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| author | Constance Alabert Carolin Loos Moritz Voelker-Albert Simona Graziano Ignasi Forné Nazaret Reveron-Gomez Lea Schuh Jan Hasenauer Carsten Marr Axel Imhof Anja Groth |
| author_facet | Constance Alabert Carolin Loos Moritz Voelker-Albert Simona Graziano Ignasi Forné Nazaret Reveron-Gomez Lea Schuh Jan Hasenauer Carsten Marr Axel Imhof Anja Groth |
| author_sort | Constance Alabert |
| collection | DOAJ |
| description | Summary: Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the histone modification landscape is challenged by incorporation of new unmodified histones during each cell cycle, and the principles governing heritability remain unclear. We take a quantitative computational modeling approach to describe propagation of histone H3K27 and H3K36 methylation states. We measure combinatorial H3K27 and H3K36 methylation patterns by quantitative mass spectrometry on subsequent generations of histones. Using model comparison, we reject active global demethylation and invoke the existence of domains defined by distinct methylation endpoints. We find that H3K27me3 on pre-existing histones stimulates the rate of de novo H3K27me3 establishment, supporting a read-write mechanism in timely chromatin restoration. Finally, we provide a detailed quantitative picture of the mutual antagonism between H3K27 and H3K36 methylation and propose that it stabilizes epigenetic states across cell division. : Alabert et al. introduce a computational model to describe the propagation of histone K27 and K36 methylations on successive generations of histones. This quantitative model invokes the existence of domains with distinct methylation endpoints and reveals that antagonisms between histone methylations enhance the stability of epigenetic states. |
| first_indexed | 2024-12-11T22:14:26Z |
| format | Article |
| id | doaj.art-53e2c297629f41bfb125891f41485232 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T22:14:26Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-53e2c297629f41bfb125891f414852322022-12-22T00:48:38ZengElsevierCell Reports2211-12472020-01-0130412231234.e8Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation LandscapesConstance Alabert0Carolin Loos1Moritz Voelker-Albert2Simona Graziano3Ignasi Forné4Nazaret Reveron-Gomez5Lea Schuh6Jan Hasenauer7Carsten Marr8Axel Imhof9Anja Groth10Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Corresponding authorHelmholtz Zentrum München-German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg 85764, Germany; Mathematical Modeling of Biological Systems, Center for Mathematics, Technische Universität München, Garching 85748, GermanyBiomedical Center, Chromatin Proteomics Group, Department of Molecular Biology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, GermanyBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; The Novo Nordisk Center for Protein Research (CPR), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkBiomedical Center, Chromatin Proteomics Group, Department of Molecular Biology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, GermanyBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; The Novo Nordisk Center for Protein Research (CPR), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkHelmholtz Zentrum München-German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg 85764, Germany; Mathematical Modeling of Biological Systems, Center for Mathematics, Technische Universität München, Garching 85748, GermanyHelmholtz Zentrum München-German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg 85764, Germany; Mathematical Modeling of Biological Systems, Center for Mathematics, Technische Universität München, Garching 85748, Germany; Faculty of Mathematics and Natural Sciences, University of Bonn, 53115 Bonn, GermanyHelmholtz Zentrum München-German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg 85764, Germany; Corresponding authorBiomedical Center, Chromatin Proteomics Group, Department of Molecular Biology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Strasse 9, 82152 Planegg-Martinsried, Germany; Corresponding authorBiotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; The Novo Nordisk Center for Protein Research (CPR), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Corresponding authorSummary: Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the histone modification landscape is challenged by incorporation of new unmodified histones during each cell cycle, and the principles governing heritability remain unclear. We take a quantitative computational modeling approach to describe propagation of histone H3K27 and H3K36 methylation states. We measure combinatorial H3K27 and H3K36 methylation patterns by quantitative mass spectrometry on subsequent generations of histones. Using model comparison, we reject active global demethylation and invoke the existence of domains defined by distinct methylation endpoints. We find that H3K27me3 on pre-existing histones stimulates the rate of de novo H3K27me3 establishment, supporting a read-write mechanism in timely chromatin restoration. Finally, we provide a detailed quantitative picture of the mutual antagonism between H3K27 and H3K36 methylation and propose that it stabilizes epigenetic states across cell division. : Alabert et al. introduce a computational model to describe the propagation of histone K27 and K36 methylations on successive generations of histones. This quantitative model invokes the existence of domains with distinct methylation endpoints and reveals that antagonisms between histone methylations enhance the stability of epigenetic states.http://www.sciencedirect.com/science/article/pii/S2211124719317176 |
| spellingShingle | Constance Alabert Carolin Loos Moritz Voelker-Albert Simona Graziano Ignasi Forné Nazaret Reveron-Gomez Lea Schuh Jan Hasenauer Carsten Marr Axel Imhof Anja Groth Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes Cell Reports |
| title | Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes |
| title_full | Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes |
| title_fullStr | Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes |
| title_full_unstemmed | Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes |
| title_short | Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes |
| title_sort | domain model explains propagation dynamics and stability of histone h3k27 and h3k36 methylation landscapes |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719317176 |
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